How Dietary Restrictions Enhance Longevity

Enhancing the activity of the enzyme GNMT has been shown to extend the lifespan of fruit flies.

AsianScientist (Oct. 27, 2015) – What are the secrets to longevity? Researchers at the University of Tokyo have found that enhancement of S-adenosylmethionine metabolism extends lifespan in fruit flies. Their research, published in Nature Communications, also identified acceleration of S-adenosylmethionine metabolism as one of the mediators of lifespan extension by dietary restriction.

Calorie restriction (CR) is known to extend lifespan in various organisms including yeast, worms, flies, mice and humans. Recent evidence indicates that quality of diet, but not the total calories, is key to this prolongation. Particularly, restriction of methionine, an essential amino acid, has been suggested to be sufficient for lifespan extension. However, the detailed molecular mechanism behind this extension is not understood.

Project Assistant Professor Fumiaki Obata and Professor Masayuki Miura in the Graduate School of Pharmaceutical Sciences, the University of Tokyo have revealed that the metabolism of S-adenosylmethionine (SAM), a metabolite synthesized from methionine, but not methionine itself, is a key factor for lifespan extension in fruit flies.

They found that adipose tissue in fruit flies has the mechanism to maintain SAM levels and identified the metabolic enzyme responsible: glycine N-methyltransferase (GNMT). In addition, older flies have higher SAM levels than young flies.

Genetically enhancing the activity of GNMT suppressed the age-dependent SAM increase and extended longevity. In addition, in flies deficient in GNMT the lifespan-extending effect of dietary restriction was abrogated, indicating that SAM metabolism is a key mediator for dietary restriction-dependent benefit.

“Since SAM metabolism is conserved in humans, this newly identified mechanism may find applications for healthy lifespan extension in our society,” said Obata. “SAM has a proven track record as an anti-depressant and supplement for treating liver damage, but little is known about its mechanism of action. This should be the focus of future research.”

The article can be found at: Obata et al. (2015) Enhancing S-Adenosyl-Methionine Catabolism Extends Drosophila Lifespan.

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Source: University of Tokyo.
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